We appreciate the thoughtful comments by Drs. Hudson, Hudson, and Schatzberg (1) on our article that was recently published in Diabetes Care (2). The authors raised several interesting questions around the relationship between hypercortisolism and depression.
The eligibility criteria for CATALYST were carefully designed to avoid potential causes for false-positive dexamethasone suppression tests (DSTs), such as acute psychiatric illness. However, psychiatric disturbances, including depression, are reported in up to 80% of patients with hypercortisolism (3). As such, it is perhaps not surprising that more than a third of CATALYST participants with hypercortisolism reported taking psychiatric medications.
In our cohort, we did not observe a difference in post-DST cortisol between participants with and without a history of depression, with a median post-DST cortisol among those with hypercortisolism and depression (n = 64) of 2.51 μg/dL (range 1.82–23.50) compared with 2.63 μg/dL (range 1.81–24.80) in those with hypercortisolism without depression (n = 188). However, this analysis was not prespecified in the study protocol, and the range is similarly broad for both groups. Depression was defined based on the participants’ medical history, and, as mentioned, participants with acute psychiatric illness were not eligible to participate in CATALYST. These factors limit the interpretation of this finding and do not exclude the possibility that post-DST cortisol may be higher in patients with acute depression.
The authors further ask whether effective treatment of depression may improve diabetes control or, vice versa, whether treatment of hypercortisolism may improve depressive symptoms. Work by others suggests that treatment of depression is associated with benefit in glycemic control (4), although we do not have direct evidence of this from our study. In response to the second part of the question, studies of mifepristone in patients with psychotic depression and other psychiatric conditions, including work by one of the authors of the letter, suggest a potential effect of mifepristone in this population (5). To our knowledge, studies of patients with combined depressive symptoms, type 2 diabetes, and hypercortisolism have not been conducted.
In summary, endogenous hypercortisolism is a multisystemic disease, and, while CATALYST focused on the impact of hypercortisolism on diabetes specifically, we agree that more work needs to be done to better understand the relationship between hypercortisolism, diabetes, and psychiatric illness.
Article Information
Acknowledgments. J.B.B. and S.E.K. are editors of Diabetes Care but were not involved in any of the decisions regarding review of the manuscript or its acceptance.
Duality of Interest. The CATALYST study was funded by Corcept Therapeutics Incorporated (Corcept). J.B.B. reports serving as an advisory panel member/consultant for Alkahest, Altimmune, Anji, Aqua Medical, AstraZeneca, Boehringer-Ingelheim, CeQur, Corcept, Eli Lilly, embecta, GentiBio, Glyscend, Insulet, Mellitus Health, Medtronic, Metsera, Novo Nordisk, Pendulum Therapeutics, Praetego, Stability Health, Terns Pharmaceuticals, Vertex Pharmaceuticals Inc., and vTv Therapeutics; research support from Corcept, Dexcom, Insulet, and Novo Nordisk; and stocks/shares in Glyscend, Mellitus Health, Pendulum Therapeutics, Praetego, and Stability Health. S.E.K. reports serving as an advisory panel member/consultant for Altpep, Amgen, Anji, Biomea Fusion, Eli Lilly, Merck, Neurimmune, and Novo Nordisk; stock options in Altpep; and research support from Corcept. T.K.S. and D.E. are employed by and own stock in Corcept. No other potential conflicts of interest relevant to this article were reported.
Handling Editors. The journal editor responsible for overseeing the review of the manuscript was M. Sue Kirkman.
Footnotes
Clinical trial reg. no. NCT05772169, clinicaltrials.gov
References
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